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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2015-00042 | Registry Identifier | NCI CTRP |
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| Name | Class |
|---|---|
| Bristol-Myers Squibb | INDUSTRY |
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The goal of this clinical research study is to find the highest tolerable dose of ipilimumab and stereotactic body radiation therapy (SBRT). The safety and effectiveness of these treatments given consecutively will also be studied.
This is an investigational study. SBRT is FDA approved for the control of metastatic and primary tumors. Ipilimumab is FDA approved and commercially available for the treatment of metastatic melanoma that cannot be removed with surgery. The use of SBRT with ipilimumab is investigational. The study doctor can explain how the study drug is designed to work.
Up to 120 participants will be enrolled in this study. All will take part at MD Anderson.
Study Groups:
Participants on this study are enrolled into Phase 1 (Dose De-Escalation, or Dose-Finding) or Phase 2 (Dose Expansion), based on when they join the study.
Phase 1: Dose De-Escalation:
If you are found to be eligible to take part in this study, you will be assigned to 1 of 5 groups based on the type of disease you have.
If you are in Group 5, SBRT will be given over a longer period of time (more days or weeks).
All participants will receive the same dose level of ipilimumab.
You will be given a separate consent form explaining SBRT and its risks.
In each group, 3 participants will be enrolled at the first dose level. If no more than 1 participant has intolerable side effects, up to 3 more participants will be enrolled at that dose level. If no intolerable side effects are seen at that dose level, that is considered the highest tolerated dose.
If enough intolerable side effects are seen at the assigned dose level, the total dose amount of radiation given in any group may be lowered up to 2 times.
Phase 2: Dose Expansion:
Once the highest tolerated dose combination is found in each study group, up to 14 more participants will be enrolled at that dose level combination in each group.
Study Drug Administration:
Each study cycle is 21 days.
If you are in Groups 1 or 3 (early ipilimumab and SBRT), you will receive ipilimumab by vein over about 90 minutes on Day 1 of all cycles. You will also receive SBRT over about 30-45 minutes on Days 1-4 of Cycle 1.
If you are in Groups 2 or 4 (late ipilimumab and SBRT), you will receive ipilimumab by vein over about 90 minutes on Day 1 of Cycles 1 and 2 and then SBRT on Days 29-33. After your SBRT treatment, you will take ipilimumab on Day 1 of Cycles 3 and 4.
If you are in Group 5 (late ipilimumab and SBRT), you will receive ipilimumab on Day 1 of Cycle 1 and SBRT over about 30-45 minutes on Days 1-5 and Days 9-12 of Cycle 1. After your SBRT treatment, you will take ipilimumab on Day 1 of Cycles 2-4.
You will be given standard drugs to help decrease the risk of side effects and to help support your immune system. You may ask the study staff for information about how the drugs are given and their risks.
Study Visits:
During Week 1 of all cycles and Week 2 of Cycle 2:
During Week 3 of Cycles 2 and 4, you will have an MRI, CT scan, and/or PET/CT scan to check the status of the disease.
If you are in Phase 2, during Week 3 of each cycle, blood (about 2 teaspoons) may be drawn for biomarker testing, if the doctor thinks it is safe.
You may have a chest scan if the doctor thinks it is needed.
Length of Study:
You may receive up to 4 cycles of treatment with ipilimumab and SBRT. About 8 weeks after you have completed Cycle 4, if the size of the tumor does not change or it gets smaller while you are receiving therapy, you may be able to continue to receive ipilimumab and/or radiation. The study doctor will discuss this option with you.
You will no longer be able to receive treatment if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after you have completed the follow-up visits.
Follow-Up:
About 30 days after your last dose of ipilimumab and then every 3 months after that for up to 2 years, you will come to the clinic for follow-up visits. At these visits:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 Liver: Concurrent (early) Ipilimumab and SBRT | Experimental | Participants with at least 1 liver metastasis - Treatment Group 1: Ipilimumab 3 mg/kg by vein on Day 1 of all 21 day cycles for a total of 4 doses. SBRT 50 Gy in 4 fractions to 1 - 4 liver lesion(s) on Days 1 - 4 of Cycle 1. |
|
| Group 2 Liver: Sequential (late) Ipilimumab and SBRT | Experimental | Participants with at least 1 liver metastasis - Treatment Group 2: Ipilimumab 3 mg/kg by vein on Day 1 of Cycles 1 and 2. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 3 and 4. Each cycle is 21 days. SBRT 50 Gy in 4 fractions to 1 - 4 liver lesion(s) on Days 29 - 33 of each 21 day cycle. |
|
| Group 3 Lung: Concurrent (early) Ipilimumab and SBRT | Experimental | Participants with at least 1 lung metastasis - Treatment Group 3: Ipilimumab 3 mg/kg by vein on Day 1 of all 21 day cycles for a total of 4 doses. SBRT 50 Gy in 4 fractions to 1 - 4 lung lesion(s) on Days 1 - 4 of Cycle 1. |
|
| Group 4 Lung: Sequential (late) Ipilimumab and SBRT | Experimental | Participants with at least 1 lung metastasis - Treatment Group 4: Ipilimumab 3 mg/kg by vein on Day 1 of Cycles 1 and 2. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 3 and 4. Each cycle is 21 days. SBRT 50 Gy in 4 fractions to 1 - 4 lung lesion(s) on Days 29 - 33 of each 21 day cycle. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ipilimumab | Drug | Treatment Group 1 and 3: Ipilimumab 3 mg/kg by vein on Day 1 of all 21 day cycles for a total of 4 doses. Treatment Group 2 and 4: Ipilimumab 3 mg/kg by vein on Day 1 of Cycles 1 and 2. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 3 and 4. Treatment Group 5: Ipilimumab 3 mg/kg by vein on Day 1 of Cycle 1. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 2-4 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Ipilimumab and Stereotactic Body Radiation Therapy (SBRT) | MTD defined as highest dose level with less than 2 patients with dose limiting toxicity (DLT) out of at least six patients in the cohort. All enrolled participants will be considered in the DLT analysis. If at any time more than or equal to one third (33%) of participants at a dose level experience DLT, the MTD will be reassessed and the next lowest dose level for the combination therapy considered the MTD. | Third week of second, 21 day cycle |
| Measure | Description | Time Frame |
|---|---|---|
| Response Rate of Ipilimumab and Stereotactic Body Radiation Therapy (SBRT) | Response and progression evaluated using guidelines proposed by the Immune Related Response Criteria (irRC). Patients with measurable disease also assessed using standard Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and World Health Organization (WHO) treatment response criteria. Complete Response (irCR): complete disappearance of all lesions (whether measurable or not, and no new lesions) confirmation by a repeat, consecutive imaging assessment no less than 4 wk from the date first documented. Partial Response (irPR): decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive imaging assessment at least 4 wk after first documentation. Progressive Disease (irPD): increase in tumor burden ≥25% relative to nadir (minimum recorded tumor burden) confirmation by a repeat, consecutive imaging assessment no less than 4 wk from date first documented. |
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| James Welsh, MD | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36921766 | Derived | He K, Hong DS, Tang C, Sezen D, Cox L, Maleki A, Bertolet G, Nguyen QN, Comeaux NI, Schuda L, Chen D, Welsh JW. Five-year overall survival with ipilimumab and stereotactic ablative radiotherapy for metastatic disease. Radiother Oncol. 2023 Jun;183:109618. doi: 10.1016/j.radonc.2023.109618. Epub 2023 Mar 13. | |
| 31996395 | Derived |
| Label | URL |
|---|---|
| University of Texas MD Anderson Cancer Center Website | View source |
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| ID | Term |
|---|---|
| D008113 | Liver Neoplasms |
| D008175 | Lung Neoplasms |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000074324 | Ipilimumab |
| D016634 | Radiosurgery |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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|
| Group 5 Liver/Lung Metastasis: (late) Ipilimumab and SBRT | Experimental | Participants with 1 liver or lung metastasis - Treatment Group 5: Ipilimumab 3 mg/kg by vein on Day 1 of Cycle 1. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 2 - 4. Each cycle is 21 days. SBRT 60 Gy in 10 fractions to 1 - 4 lung, liver, or adrenal lesion (s) on Days 1 - 5 and Days 9 - 12 of Cycle 1. |
|
| Thyroid Expansion Cohort | Experimental | Participants enrolled in this arm treated to a total dose of 50 Gy in 4 fractions, 60 Gy in 10 fractions, or 20 Gy in 5 fractions with stereotactic radiotherapy to a liver or lung lesion. The choice of radiation dose will be at the discretion of the treating radiation oncologist. Participants receive Ipilimumab every 21 days for a total of 4 doses. |
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|
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| Stereotactic Body Radiation Therapy (SBRT) | Radiation | Treatment Group 1 and 3: SBRT 50 Gy in 4 fractions to 1 - 4 liver lesion(s) on Days 1 - 4 of Cycle 1. Treatment Group 2 and 4: SBRT 50 Gy in 4 fractions to 1-4 liver lesion(s) on Days 29 - 33 of each 21 day cycle. Treatment Group 5: SBRT 60 Gy in 10 fractions to 1 - 4 lung, liver, or adrenal lesion (s) on Days 1 - 5 and Days 9 - 12 of Cycle 1. |
|
|
| 30 days after last dose of Ipilimumab |
| Chen D, Menon H, Verma V, Guo C, Ramapriyan R, Barsoumian H, Younes A, Hu Y, Wasley M, Cortez MA, Welsh J. Response and outcomes after anti-CTLA4 versus anti-PD1 combined with stereotactic body radiation therapy for metastatic non-small cell lung cancer: retrospective analysis of two single-institution prospective trials. J Immunother Cancer. 2020 Jan;8(1):e000492. doi: 10.1136/jitc-2019-000492. |
| 27240885 | Derived | Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet. 2016 Dec 3;388(10061):2783-2795. doi: 10.1016/S0140-6736(16)30172-6. Epub 2016 May 27. |
| D008107 |
| Liver Diseases |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D013238 | Stereotaxic Techniques |
| D019635 | Neurosurgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |